Next-generation sequencing in the evaluation of biliary strictures in patients with primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a well-described risk factor for the development of cholangiocarcinoma (CCA). Early detection of CCA in these patients is of great importance because it expands options for therapeutic interventions, including liver transplantation. Current diagnostic tests for the evaluation of biliary strictures are limited to biliary brushing (BB) cytology and fluorescence in situ hybridization (FISH). Next-generation sequencing (NGS) has become an important diagnostic tool in oncology and may be a useful tool for diagnosing CCA on BBs. It is not clear how NGS performs when it is added to BB cytology and FISH in patients with PSC.

This study reports the authors' experience with NGS performed as a prospective cotest with cytology and FISH on BBs obtained from 60 patients with PSC followed at Massachusetts General Hospital. A duct with malignancy was defined as a high-risk (HR) stricture with either high-grade dysplasia or CCA.

NGS was better than FISH and cytology in detecting HR strictures, which showed multiple genetic mutations in all cases. NGS provided specific mutational information, and NGS results were reproducible in longitudinal samples.

Adding NGS to BB cytology and FISH in the evaluation of biliary strictures for patients with PSC may provide additional information that could help to inform clinical management.